Recent studies demonstrate that simian virus 40 (SV40) induces a change during transformation of hamster cells resulting in transformed (tf) cell resistance to lysis by activated macrophages (AM) in vitro (nonlytic tf cell phenotype). SV40-tf mounse or rat cells and adenovirus (Ad)2-tf hamster cells are highly susceptible to lysis by AM (lytic tf cell phenotype). In vivo data suggest a positive correlation between the nonlytic phenotype and tf cell resistance to allograft rejection. The host restriction and virus specificity of the nonlytic cell phenotype will be studied by transforming cells from different inbred hamster strains with several DNA viruses, i.e., Ad2, SV40, Ad12, polyoma, bovine papilloma, and BK viruses. Sensitivity of these virus-tf lines to AM-induced lysis will be compared to that of sensitive and resistant lines in radiorelease assays. The broader immunological significance of the nonlytic target cell phenotype will be explored by quantitating lysis of these cell lines following exposure to other classes of hamster effector cells, i.e., natural cytotoxic cells, cytotoxic lymphocytes, and different effector cells in the presence of specific antibody. Studies aimed at defining the role of viral genome function in expression of lytic or nonlytic target cell response to injury by effector cells will be performed using, as targets, hamster cells transformed by SV40 early function viral mutants and SV40 infected Ad2-tf cells. The dominant or recessive nature of the nonlytic phenotype will be studied using somatic cell hybrids between SV40-tf and Ad2-tf hamster cells. The possibility that SV40-tf hamster cells may inhibit AM tumoricidal function will be evaluated by determining the effects of these resistant targets or their products on Am-induced lysis of sensitive target cells. Target cell response to injury by these effector cell populations will be related to tumor inducing capacity of tf cells in syngeneic and allogeneic hosts. Studies of tf cells with nonlytic responses to effector cell injury may reveal novel mechanisms employed by tumor cells to evade immune surveillance and may provide a basis for alterations in the tumor microenvironment to promote more efficient destruction of relatively resistant tumor cells.